1. Field of the Invention
This invention relates to atrial natriuretic factor which is encapsulated within acidic proteinoid microspheres and to the periodic oral administration of same to warm blooded animals to control blood pressure.
2. Description of the Prior Art
Atrial natriuretic factor, which is commonly abbreviated ANF, is a polypeptide material which is believed to be produced in the atrium of the mammalian heart and which is known to be a powerful diuretic and blood pressure regulator. Because of the minute quantities of ANF found in mammals, it has been difficult to extract sufficient quantities from domestic animal carcasses to comprehensively study the effect of administering ANF to living mammals and totally impractical to use such animal extract as a primary diuretic and blood pressure depressant. However, genetically engineered ANF has recently become available in larger quantities and extensive research has been undertaken on the therepeutic use of this material.
Similar to many other endogenous polypeptides, unprotected ANF is rapidly degraded in the gastrointestinal tract and is absorbed poorly through the gastrointestinal mucosa. Its administration has, heretofore, been limited to intravenous injection.
Recent studies have shown that the intravenous administration to hypertensive rats of single large doses of ANF produce initial large reductions in blood pressure, but that this effect is transient. Significant reductions in blood pressure have been achieved for periods that seldom exceed about twenty minutes and, regardless of dosage, blood pressures return to essentially pre-dosage levels in less than thirty minutes. This exceedingly short duration of effectiveness has been attributed to the fact that ANF in the bloodstream is rapidly inactivated or removed by the kidneys. Thus, in order to maintain the effective presence of ANF in the bloodstream, it has been found that it must be repeatedly injected at short intervals and that its anti-hypertensive effect is most pronounced when continuously infused.
This obviously is not practical for chronic therapy and there is a need for a means for delivering ANF to the bloodstream which will sustain it at an effective level for reducing blood pressure for a period that is sufficiently long to permit periodic administration at reasonable intervals.
U.S. patent application Ser. No. 98,027, issued as U.S. Pat. No. 4,925,673 the disclosure of which is incorporated herein by reference, describes orally administerable compositions for delivering a gastrointestinally labile or poorly absorbed pharmacological agent to the bloodstream in physiologically active form. The active agent in these compositions is microencapsulated within hollow acidic proteinoid microspheres which are stable in acid environments and resistant to gastrointestinal enzymes, but which dissolve at the near neutral pH of the blood. These hollow microspheres protect the encapsulated pharmacological agent in the acidic portions of the gastrointestinal tract and those microspheres having a diameter of less than about 10 microns readily penetrate the gastrointestinal mucosa and release the agent in the bloodstream.